Yifeng Wang

Zijie Fang, Yihan Liu, Yifeng Wang et al.

Biomarker detection is an indispensable part in the diagnosis and treatment of low-grade glioma (LGG). However, current LGG biomarker detection methods rely on expensive and complex molecular genetic testing, for which professionals are required to analyze the results, and intra-rater variability is often reported. To overcome these challenges, we propose an interpretable deep learning pipeline, a Multi-Biomarker Histomorphology Discoverer (Multi-Beholder) model based on the multiple instance learning (MIL) framework, to predict the status of five biomarkers in LGG using only hematoxylin and eosin-stained whole slide images and slide-level biomarker status labels. Specifically, by incorporating the one-class classification into the MIL framework, accurate instance pseudo-labeling is realized for instance-level supervision, which greatly complements the slide-level labels and improves the biomarker prediction performance. Multi-Beholder demonstrates superior prediction performance and generalizability for five LGG biomarkers (AUROC=0.6469-0.9735) in two cohorts (n=607) with diverse races and scanning protocols. Moreover, the excellent interpretability of Multi-Beholder allows for discovering the quantitative and qualitative correlations between biomarker status and histomorphology characteristics. Our pipeline not only provides a novel approach for biomarker prediction, enhancing the applicability of molecular treatments for LGG patients but also facilitates the discovery of new mechanisms in molecular functionality and LGG progression.

Ye Zhang, Yifeng Wang, Zijie Fang et al.

Weakly supervised segmentation methods have gained significant attention due to their ability to reduce the reliance on costly pixel-level annotations during model training. However, the current weakly supervised nuclei segmentation approaches typically follow a two-stage pseudo-label generation and network training process. The performance of the nuclei segmentation heavily relies on the quality of the generated pseudo-labels, thereby limiting its effectiveness. This paper introduces a novel domain-adaptive weakly supervised nuclei segmentation framework using cross-task interaction strategies to overcome the challenge of pseudo-label generation. Specifically, we utilize weakly annotated data to train an auxiliary detection task, which assists the domain adaptation of the segmentation network. To enhance the efficiency of domain adaptation, we design a consistent feature constraint module integrating prior knowledge from the source domain. Furthermore, we develop pseudo-label optimization and interactive training methods to improve the domain transfer capability. To validate the effectiveness of our proposed method, we conduct extensive comparative and ablation experiments on six datasets. The results demonstrate the superiority of our approach over existing weakly supervised approaches. Remarkably, our method achieves comparable or even better performance than fully supervised methods. Our code will be released in https://github.com/zhangye-zoe/DAWN.

Zijie Fang, Yifeng Wang, Peizhang Xie et al.

Tissue semantic segmentation is one of the key tasks in computational pathology. To avoid the expensive and laborious acquisition of pixel-level annotations, a wide range of studies attempt to adopt the class activation map (CAM), a weakly-supervised learning scheme, to achieve pixel-level tissue segmentation. However, CAM-based methods are prone to suffer from under-activation and over-activation issues, leading to poor segmentation performance. To address this problem, we propose a novel weakly-supervised semantic segmentation framework for histopathological images based on image-mixing synthesis and consistency regularization, dubbed HisynSeg. Specifically, synthesized histopathological images with pixel-level masks are generated for fully-supervised model training, where two synthesis strategies are proposed based on Mosaic transformation and Bézier mask generation. Besides, an image filtering module is developed to guarantee the authenticity of the synthesized images. In order to further avoid the model overfitting to the occasional synthesis artifacts, we additionally propose a novel self-supervised consistency regularization, which enables the real images without segmentation masks to supervise the training of the segmentation model. By integrating the proposed techniques, the HisynSeg framework successfully transforms the weakly-supervised semantic segmentation problem into a fully-supervised one, greatly improving the segmentation accuracy. Experimental results on three datasets prove that the proposed method achieves a state-of-the-art performance. Code is available at https://github.com/Vison307/HisynSeg.

Xingyue Huang, Rishabh, Gregor Franke et al.

Recent advances in Large Language Models (LLMs) have shown that their reasoning capabilities can be significantly improved through Reinforcement Learning with Verifiable Reward (RLVR), particularly in domains like mathematics and programming, where ground-truth correctness can be automatically evaluated. However, extending this success to other reasoning-intensive domains remains challenging due to the scarcity of high-quality, verifiable datasets and the high cost of human supervision. In this work, we introduce the Loong Project: an open-source framework for scalable synthetic data generation and verification across a diverse range of reasoning-intensive domains. The framework consists of two key components: (1) LoongBench, a curated seed dataset containing 8,729 human-vetted examples across 12 domains (e.g., Advanced Mathematics, Chemistry, Logic), each paired with executable code and rich metadata; and (2) LoongEnv, a modular synthetic data generation environment that supports multiple prompting strategies to produce new question-answer-code triples. Together, these components form an agent-environment loop that enables reinforcement learning, where an LLM-based agent is rewarded for generating Chain-of-Thought (CoT) solutions that align with code-executed answers. Empirically, we benchmark LoongBench on a broad suite of both open-source and proprietary LLMs to evaluate domain coverage and reveal performance bottlenecks. In addition, we conduct a comprehensive analysis of synthetic data generated by LoongEnv, examining correctness, difficulty, and diversity. Code and documentation are available at https://github.com/camel-ai/loong.

Ye Zhang, Yu Zhou, Yifeng Wang et al.

Cell instance segmentation is critical to analyzing biomedical images, yet accurately distinguishing tightly touching cells remains a persistent challenge. Existing instance segmentation frameworks, including detection-based, contour-based, and distance mapping-based approaches, have made significant progress, but balancing model performance with computational efficiency remains an open problem. In this paper, we propose a novel cell instance segmentation method inspired by the four-color theorem. By conceptualizing cells as countries and tissues as oceans, we introduce a four-color encoding scheme that ensures adjacent instances receive distinct labels. This reformulation transforms instance segmentation into a constrained semantic segmentation problem with only four predicted classes, substantially simplifying the instance differentiation process. To solve the training instability caused by the non-uniqueness of four-color encoding, we design an asymptotic training strategy and encoding transformation method. Extensive experiments on various modes demonstrate our approach achieves state-of-the-art performance. The code is available at https://github.com/zhangye-zoe/FCIS.

Songhan Jiang, Zhengyu Gan, Linghan Cai et al.

Survival prediction, utilizing pathological images and genomic profiles, is increasingly important in cancer analysis and prognosis. Despite significant progress, precise survival analysis still faces two main challenges: (1) The massive pixels contained in whole slide images (WSIs) complicate the process of pathological images, making it difficult to generate an effective representation of the tumor microenvironment (TME). (2) Existing multimodal methods often rely on alignment strategies to integrate complementary information, which may lead to information loss due to the inherent heterogeneity between pathology and genes. In this paper, we propose a Multimodal Cross-Task Interaction (MCTI) framework to explore the intrinsic correlations between subtype classification and survival analysis tasks. Specifically, to capture TME-related features in WSIs, we leverage the subtype classification task to mine tumor regions. Simultaneously, multi-head attention mechanisms are applied in genomic feature extraction, adaptively performing genes grouping to obtain task-related genomic embedding. With the joint representation of pathological images and genomic data, we further introduce a Transport-Guided Attention (TGA) module that uses optimal transport theory to model the correlation between subtype classification and survival analysis tasks, effectively transferring potential information. Extensive experiments demonstrate the superiority of our approaches, with MCTI outperforming state-of-the-art frameworks on three public benchmarks. \href{https://github.com/jsh0792/MCTI}{https://github.com/jsh0792/MCTI}.

Ziyue Wang, Ye Zhang, Yifeng Wang et al.

Deep learning has achieved impressive results in nuclei segmentation, but the massive requirement for pixel-wise labels remains a significant challenge. To alleviate the annotation burden, existing methods generate pseudo masks for model training using point labels. However, the generated masks are inevitably different from the ground truth, and these dissimilarities are not handled reasonably during the network training, resulting in the subpar performance of the segmentation model. To tackle this issue, we propose a framework named DoNuSeg, enabling \textbf{D}ynamic pseudo label \textbf{O}ptimization in point-supervised \textbf{Nu}clei \textbf{Seg}mentation. Specifically, DoNuSeg takes advantage of class activation maps (CAMs) to adaptively capture regions with semantics similar to annotated points. To leverage semantic diversity in the hierarchical feature levels, we design a dynamic selection module to choose the optimal one among CAMs from different encoder blocks as pseudo masks. Meanwhile, a CAM-guided contrastive module is proposed to further enhance the accuracy of pseudo masks. In addition to exploiting the semantic information provided by CAMs, we consider location priors inherent to point labels, developing a task-decoupled structure for effectively differentiating nuclei. Extensive experiments demonstrate that DoNuSeg outperforms state-of-the-art point-supervised methods. The code is available at https://github.com/shinning0821/MICCAI24-DoNuSeg.

Yifeng Wang, Ke Chen, Haohan Wang · cmu

Automated diagnosis of Alzheimer Disease(AD) from brain imaging, such as magnetic resonance imaging (MRI), has become increasingly important and has attracted the community to contribute many deep learning methods. However, many of these methods are facing a trade-off that 3D models tend to be complicated while 2D models cannot capture the full 3D intricacies from the data. In this paper, we introduce a new model structure for diagnosing AD, and it can complete with performances of 3D models while essentially is a 2D method (thus computationally efficient). While the core idea lies in new perspective of cutting the 3D images into multiple 2D slices from three dimensions, we introduce multiple components that can further benefit the model in this new perspective, including adaptively selecting the number of sclices in each dimension, and the new attention mechanism. In addition, we also introduce a morphology augmentation, which also barely introduces new computational loads, but can help improve the diagnosis performances due to its alignment to the pathology of AD. We name our method ADAPT, which stands for Alzheimer Diagnosis through Adaptive Profiling Transformers. We test our model from a practical perspective (the testing domains do not appear in the training one): the diagnosis accuracy favors our ADAPT, while ADAPT uses less parameters than most 3D models use.